Dr. Elissa Wilker's long term career goal is to become an independent investigator capable of leading studies on environmental impacts and brain activity. The objective of this research proposal is to elucidate the impact of traffic pollution o brain structure and cognitive function in a population that includes individuals with mild memory complaints or early dementia. During the mentored (K99) phase of this award, the applicant will gain expertise conducting studies of the chronic effects of air pollution on cognitive decline and small vessel disease, as assessed by neuroimaging. She will also receive training in the areas of neuroepidemiology, neuroscience and dementia, advanced statistical methodology and exposure assessment. Dr. Murray Mittleman will serve as the Primary Mentor for this award and will oversee all aspects of Dr. Wilker's training. Dr. Mittleman has a unique expertise in environmental epidemiology, biological mechanisms, and statistical methods that will make him an ideal coordinator for the mentorship team. He also has extensive mentorship experience and will provide primary support for career development. In addition, Dr. Wilker will be co-mentored by Dr. Deborah Blacker and Dr. Anand Viswanathan in order to receive specific training in neuroepidemiology, neuroimaging methodologies and their clinical interpretation. Dr. Wilker will also have support in environmental-and neuro-statistical methods as well as environmental exposure assessment. During the independent phase (R00) phase of this award, the applicant will investigate associations between traffic exposures and novel neuroimaging measures of cortical morphology and amyloid deposition. The proposed research uses detailed individual-level estimates of long term exposure to traffic pollution and state of the art neuroimaging to study the effects of traffic on the brain in a population with mild cognitive impairment. This work will provide a first step in developing a comprehensive approach to identify environmental risk factors of structural changes in the brain and declines in cognitive function. The findings from this program of research will elucidate understanding the underlying vascular and non-vascular mechanisms of air pollution effects on the brain in a population at risk for further cognitive decline and dementia.